In 1985, drug smuggler Andrew C. Thornton II drops a shipment of cocaine from his plane. He attempts to parachute out with a drug-filled duffel bag, but knocks himself unconscious on the doorframe, causing him to fall to his death. His body lands in Knoxville, Tennessee, where he is identified by Bob, a local detective. He concludes that the cocaine is likely from St. Louis drug kingpin Syd White, and the remainder is missing. Meanwhile, in the Chattahoochee-Oconee National Forest, an American black bear eats some of the cocaine, becoming highly aggressive and attacking two hikers, Elsa and Olaf, killing the former.In northeast Georgia, middle schooler Dee Dee lives with her mother, nurse Sari. Dee Dee skips school with her best friend Henry in order to paint a picture of the falls in the forest. On the trail to the falls, they find a lost brick of cocaine and ingest some before they are attacked by the bear. Sari ventures into the forest to search for the children with Liz, a park ranger, and Peter, a wildlife activist. They find Henry clinging to a tree, hiding from the bear. The bear attacks, sending Peter stumbling through a pile of cocaine and slashing Liz in the process. The bear tries to climb a tree and attack Henry but gets attracted to a cocaine-coated Peter. Ignoring Henry, the bear kills Peter. Sari and Henry flee deeper into the forest, and Liz sends for help.In St. Louis, Syd sends his fixer Daveed to recover the remaining cocaine. Daveed travels to Georgia with Eddie, Syd's son, who has grown depressed following the death of his wife and has abandoned his own son. They arrive in Georgia, as does Bob. At the forest station, Daveed gets into a fight with the Duchamps gang, three delinquents who cause trouble in the forest. After Daveed beats them, one of the members, Stache, agrees to take Daveed and Eddie to recover some of the cocaine he stashed in a gazebo. Liz arrives back at the station, pursued by the bear. Liz accidentally kills Ponytail, one of the Duchamps, before the bear slaughters Vest, another of the Duchamps gang. Paramedics Beth and Tom arrive and collect Liz after a brief skirmish with the bear. They leave with Liz in an ambulance, but the bear pursues and jumps into the vehicle. In the ensuing chaos, Tom is killed by the bear, while Liz falls out of the ambulance and is dragged to death on the road. Beth loses control of the ambulance and crashes into a tree, causing her to fly through the windshield to her death.Sari and Henry discover that Dee Dee left a trail of paint which they use to track her. Daveed and Eddie are taken to the gazebo but when they encounter Bob there with the stashed duffel of cocaine, Bob wounds Daveed. The bear appears, but Bob distracts it with the bag of coke. Bob is suddenly shot fatally by Syd, who reveals that he is under pressure from his superiors to retrieve the cocaine.Sari and Henry find Olaf, who is mourning Elsa; Olaf leads them to Dee Dee's hiding place in the bear's cave which contains two cubs, revealing that the bear is a mother. Olaf leaves and is killed by the bear. Syd, Eddie, and Daveed find the cave, which leads out to a ledge behind the falls. The bear returns to the cave. Sari, Henry, and Dee Dee jump into the water below to safety, followed by Eddie and Daveed, who have chosen to quit the drug business together, and they all survive. However, Syd refuses to leave the bag of cocaine found in the cave. He shoots and wounds the bear but is unsuccessful in killing it and is disemboweled by the bear and her cubs.Later, Stache hitchhikes to New York with a duffel bag of cocaine, while Eddie, accompanied by Daveed and Bob's dog, reunites with his son.